Synergistic anticancer activity by co-delivered nanosized dual therapeutic agents and siRNA in colon cancer

Abstract

Co-delivery of anticancer drugs and nucleic acid can improve therapeutic potential by modulating apoptosis pathways for the treatment of cancer. We synthesized an amphiphilic carrier to encapsulate two drugs and one siRNA for co-delivering nanoparticles (NPs) to colon cancer cells. NPs carrying multiple drugs along with siRNA is challenging and thus, rare in literature. Therefore, anticancer efficacy and synergy between multiple drugs and siRNA are important to study. Specifically, in this study, NP containing doxorubicin (DOX), aspirin (Asp) and siRNA targeting BCL-2 were prepared and characterized. The NPs demonstrated enhanced anticancer activity against the colon cancer cell line (HCT-116) compared to other cancer cell lines. Multiple drugs (DOX and Asp) and BCL-2 siRNA loaded NPs synergistically induced apoptosis in HCT-116 cells as evident by an increase in G2/M phase cells and decrease in mitochondrial membrane potential (MMP). Chou-Talalay analysis revealed strong synergistic interaction in all doses of NPs. Therefore, multiple drugs and siRNA loaded NPs significantly inhibited HCT-116 cell growth and hence could be a potential candidate for the treatment of colon cancer.